{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:31:12Z","timestamp":1792729872923,"version":"4.5.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Matrix metalloproteinases MMP-2 and MMP-9 modulate inflammatory processes at the blood\u2013brain barrier (BBB), but their presence and function in the dura mater remain unclear. We therefore investigated their contribution to immune regulation at this site during neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed dura mater from na\u00efve and experimental autoimmune encephalomyelitis (EAE) mice using immunofluorescence, gelatin zymography, flow cytometry, and single-nucleus RNA sequencing (snRNA-seq). Comparisons were performed between wild-type (WT) and\n                      <jats:italic>Mmp9<\/jats:italic>\n                      -\/- mice to define gelatinase expression, cellular sources, transcriptional alterations, and immune cell dynamics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pro- and activated-MMP-2 and MMP-9 were detectable in na\u00efve dura, with selective upregulation of MMP-9 during EAE.\n                      <jats:italic>Mmp9<\/jats:italic>\n                      -\/- mice demonstrated delayed EAE onset but more severe disease at peak. SnRNA-seq revealed that\n                      <jats:italic>Mmp9<\/jats:italic>\n                      deficiency altered endothelial transcriptional programs, especially in venous endothelial cells, and promoted expansion of granulocyte populations with mature neutrophil signatures. Flow cytometry and immunofluorescence confirmed increased Ly6C\u207aLy6G\u207a neutrophils in\n                      <jats:italic>Mmp9<\/jats:italic>\n                      -\/- dura during EAE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that MMP-9 regulates immune cell composition and activation within the dura during neuroinflammation. While\n                      <jats:italic>Mmp9<\/jats:italic>\n                      deficiency delays disease onset, it enhances neutrophil accumulation and inflammatory responses at this CNS border, suggesting a previously unrecognized, potentially anti-inflammatory role for MMP-9 in the dura.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1713166","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T06:30:43Z","timestamp":1765434643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["MMP-9 affects dural cell composition and granulocyte accumulation during neuroinflammation"],"prefix":"10.3389","volume":"16","author":[{"given":"Sheng-Hsiang","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Gerwien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Burmeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Tsang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Na","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"B\u00f6rsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Sorokin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Meyer zu H\u00f6rste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)02023-3","article-title":"Gelatinase B: a tuner and amplifier of immune functions","volume":"22","author":"Opdenakker","year":"2001","journal-title":"Trends Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2013.770819","article-title":"Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): The next decade","volume":"48","author":"Vandooren","year":"2013","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/path.4493","article-title":"Stromal matrix metalloproteinase 2 regulates collagen expression and promotes the outgrowth of experimental metastases","volume":"235","author":"Bates","year":"2015","journal-title":"J Pathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.092","article-title":"Endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration","volume":"18","author":"Song","year":"2017","journal-title":"Cell Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21491","article-title":"Matrix metalloproteinases*","volume":"274","author":"Nagase","year":"1999","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.bbamcr.2009.09.015","article-title":"Matrix metalloproteinases: What do they not do? 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